NGR-TNF in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00098943

Last Updated: 2012-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30

Brief Summary

RATIONALE: Targeted therapy with tumor necrosis factor combined with a fusion protein may stop the growth of solid tumors by stopping blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of NGR-TNF in treating patients with advanced solid tumors.

Detailed Description

OBJECTIVES:

Primary

• Determine the dose-limiting toxicity and maximum tolerated dose of tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) in patients with advanced solid tumors.
• Determine the recommended phase II dose of this drug in these patients.

Secondary

• Determine the mechanism of action of this drug in these patients.
• Determine response in patients treated with this drug.

OUTLINE: This is an open-label, nonrandomized, dose-escalation, multicenter study.

Patients receive tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) IV over 1 hour on day 1. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 1-6 patients receive escalating doses of NGR-TNF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients receive treatment at the MTD.

Patients are followed every 8 weeks until disease progression or the start of a new anticancer treatment.

PROJECTED ACCRUAL: A total of 1-30 patients will be accrued for this study.

Conditions

Colorectal Cancer; Head and Neck Cancer; Kidney Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific; stage IV renal cell cancer; recurrent renal cell cancer; stage IV colon cancer; recurrent colon cancer; anaplastic thyroid cancer; insular thyroid cancer; thyroid gland medullary carcinoma; stage IV follicular thyroid cancer; stage IV papillary thyroid cancer; recurrent thyroid cancer; recurrent squamous cell carcinoma of the hypopharynx; recurrent squamous cell carcinoma of the larynx; recurrent squamous cell carcinoma of the lip and oral cavity; recurrent squamous cell carcinoma of the nasopharynx; recurrent squamous cell carcinoma of the oropharynx; recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity; stage IV squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the nasopharynx; stage IV squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity; recurrent verrucous carcinoma of the larynx; recurrent verrucous carcinoma of the oral cavity; stage IV verrucous carcinoma of the oral cavity; stage IV verrucous carcinoma of the larynx; recurrent adenoid cystic carcinoma of the oral cavity; stage IV adenoid cystic carcinoma of the oral cavity; recurrent basal cell carcinoma of the lip; stage IV basal cell carcinoma of the lip; recurrent mucoepidermoid carcinoma of the oral cavity; stage IV mucoepidermoid carcinoma of the oral cavity; recurrent lymphoepithelioma of the nasopharynx; recurrent lymphoepithelioma of the oropharynx; stage IV lymphoepithelioma of the nasopharynx; stage IV lymphoepithelioma of the oropharynx; recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity; stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity; recurrent inverted papilloma of the paranasal sinus and nasal cavity; recurrent midline lethal granuloma of the paranasal sinus and nasal cavity; stage IV inverted papilloma of the paranasal sinus and nasal cavity; stage IV midline lethal granuloma of the paranasal sinus and nasal cavity; metastatic parathyroid cancer; recurrent parathyroid cancer; recurrent salivary gland cancer; stage IV salivary gland cancer

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

CNGRC peptide-TNF alpha conjugate

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of advanced solid tumor not amenable to any clinical improvement by current standard treatments

• Preferably tumors well known to be very angiogenic (e.g., renal, colon, thyroid, and head and neck cancers)
• No clinical signs of CNS involvement

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-2 OR
• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST and/or ALT < 2.5 times ULN (5 times ULN in the presence of liver metastases)

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• Cardiac function normal
• No uncontrolled hypertension
• No condition in which hypovolemia and its consequences (e.g., increased stroke volume, elevated blood pressure) or hemodilution could represent a risk to the patient

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No active or uncontrolled systemic infection
• No other uncontrolled disease, serious illness, or medical condition that would preclude study participation
• No known hypersensitivity/allergic reaction to human albumin preparations or any of the excipients
• No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 28 days since prior immunotherapy

Chemotherapy

• At least 28 days since prior chemotherapy and recovered

Endocrine therapy

• At least 28 days since prior hormonal therapy

Radiotherapy

• At least 28 days since prior radiotherapy and recovered
• No prior radiotherapy to > 25% of bone marrow reserve

Surgery

• More than 2 weeks since prior surgery

Other

• No other concurrent anticancer therapy
• No other concurrent investigational agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cornelis J. A. Punt, MD, PhD

Role: STUDY_CHAIR

Universitair Medisch Centrum St. Radboud - Nijmegen

Locations

University Medical Center Hamburg - Eppendorf

Hamburg, , Germany

Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, , Netherlands

Countries

Germany; Netherlands

References

van Laarhoven HW, Fiedler W, Desar IM, van Asten JJ, Marreaud S, Lacombe D, Govaerts AS, Bogaerts J, Lasch P, Timmer-Bonte JN, Lambiase A, Bordignon C, Punt CJ, Heerschap A, van Herpen CM. Phase I clinical and magnetic resonance imaging study of the vascular agent NGR-hTNF in patients with advanced cancers (European Organization for Research and Treatment of Cancer Study 16041). Clin Cancer Res. 2010 Feb 15;16(4):1315-23. doi: 10.1158/1078-0432.CCR-09-1621. Epub 2010 Feb 9.

Reference Type: RESULT

PMID: 20145168 (View on PubMed)

Van Laarhoven H, Fiedler W, Desar IM, et al.: Phase I and DCE-MRI evaluation of NGR-TNF, a novel vascular targeting agent, in patients with solid tumors (EORTC 16041). [Abstract] J Clin Oncol 26 (Suppl 15): A-3521, 2008.

Reference Type: RESULT

Heerschap A, Fiedler W, Marreaud S, et al.: A phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041). [Abstract] J Clin Oncol 25 (Suppl 18): A-14074, 2007.

Reference Type: RESULT

van Herpen C, Fiedler W, Marreaud S, et al.: A biological and pharmacologic phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041). [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-B78, 2007.

Reference Type: RESULT

van Herpen C, Fiedler W, Toma S, et al.: Phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumours (EORTC 16041). [Abstract] European Journal of Cancer Supplements 4 (12): A-366, 113, 2006.

Reference Type: RESULT

Other Identifiers

EORTC-16041

Identifier Type: -

Identifier Source: secondary_id

MOLMED-EORTC-16041

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2004-000950-21

Identifier Type: -

Identifier Source: secondary_id

EORTC-16041

Identifier Type: -

Identifier Source: org_study_id